WO2004082618A3 - Synthesis of 5-azacytidine - Google Patents

Synthesis of 5-azacytidine Download PDF

Info

Publication number
WO2004082618A3
WO2004082618A3 PCT/US2004/007894 US2004007894W WO2004082618A3 WO 2004082618 A3 WO2004082618 A3 WO 2004082618A3 US 2004007894 W US2004007894 W US 2004007894W WO 2004082618 A3 WO2004082618 A3 WO 2004082618A3
Authority
WO
WIPO (PCT)
Prior art keywords
azacytidine
synthesis
azacytosine
coupling
silylation
Prior art date
Application number
PCT/US2004/007894
Other languages
French (fr)
Other versions
WO2004082618A2 (en
Inventor
Dumitru Ionescu
Peter Blumbergs
Original Assignee
Ash Stevens Inc
Dumitru Ionescu
Peter Blumbergs
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ash Stevens Inc, Dumitru Ionescu, Peter Blumbergs filed Critical Ash Stevens Inc
Publication of WO2004082618A2 publication Critical patent/WO2004082618A2/en
Publication of WO2004082618A3 publication Critical patent/WO2004082618A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/12—Triazine radicals

Abstract

The present invention provides a method for the preparation of 5-azacytidine, wherein 5-azacytidine is represented by the structure: The method involves the silylation of 5-azacytosine, followed by the coupling of silylated 5-azacytosine to a protected β-D-ribofuranose derivative. The coupling reaction is catalyzed by trimethylsilyl trifluoromethanesulfonate (TMS-Triflate).
PCT/US2004/007894 2003-03-17 2004-03-16 Synthesis of 5-azacytidine WO2004082618A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/390,526 2003-03-17
US10/390,526 US7038038B2 (en) 2003-03-17 2003-03-17 Synthesis of 5-azacytidine

Publications (2)

Publication Number Publication Date
WO2004082618A2 WO2004082618A2 (en) 2004-09-30
WO2004082618A3 true WO2004082618A3 (en) 2004-12-29

Family

ID=32987548

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/007894 WO2004082618A2 (en) 2003-03-17 2004-03-16 Synthesis of 5-azacytidine

Country Status (2)

Country Link
US (5) US7038038B2 (en)
WO (1) WO2004082618A2 (en)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6887855B2 (en) 2003-03-17 2005-05-03 Pharmion Corporation Forms of 5-azacytidine
US6943249B2 (en) 2003-03-17 2005-09-13 Ash Stevens, Inc. Methods for isolating crystalline Form I of 5-azacytidine
US7038038B2 (en) * 2003-03-17 2006-05-02 Pharmion Corporation Synthesis of 5-azacytidine
US8916552B2 (en) 2006-10-12 2014-12-23 Astex Therapeutics Limited Pharmaceutical combinations
WO2008044045A1 (en) 2006-10-12 2008-04-17 Astex Therapeutics Limited Pharmaceutical combinations
CN101311184B (en) * 2007-05-25 2011-05-04 上海医药工业研究院 2-deoxy-D-ribose derivates, preparation method and use thereof
BRPI0817234A2 (en) * 2007-09-26 2014-09-30 Sinai School Medicine AZACITIDINE ANALOGS AND ITS USES
CN101821278B (en) * 2008-01-03 2012-03-28 南京华狮化工有限公司 Synthesis method of decitabine
DK2695609T3 (en) 2008-05-15 2020-02-10 Celgene Corp Oral formulations of cytidine analogues and methods for their use
WO2010014883A2 (en) 2008-08-01 2010-02-04 Dr. Reddy's Laboratories Ltd. Azacitidine process and polymorphs
EP2324042B1 (en) * 2008-08-06 2012-11-28 Sicor, Inc. Process for preparing azacytidine intermediate
JP5650643B2 (en) * 2008-08-08 2015-01-07 サイノファーム タイワン リミテッド Method for producing 5-azacytosine nucleoside and derivatives thereof
US8586729B2 (en) * 2008-10-03 2013-11-19 Scinopharm Taiwan Ltd. Synthesis of decitabine
CA2755976C (en) 2009-03-23 2020-04-07 Ambit Biosciences Corporation Methods of treatment using combination therapy
US20100249394A1 (en) * 2009-03-26 2010-09-30 Albemarle Corporation Processes for producing decitabine
EP2424845A4 (en) * 2009-04-27 2014-03-05 Reddys Lab Ltd Dr Preparation of decitabine
IT1399195B1 (en) 2010-03-30 2013-04-11 Chemi Spa PROCESS FOR THE SYNTHESIS OF AZACITIDINE AND DECITABINE
CN101974051B (en) * 2010-10-08 2012-08-08 重庆泰濠制药有限公司 Method for synthesizing azacitidine
CA2825152A1 (en) 2011-01-31 2012-08-09 Celgene Corporation Pharmaceutical compositions of cytidine analogs and methods of use thereof
CN103619864A (en) 2011-03-31 2014-03-05 细胞基因国际有限公司 Systhesis of 5-azacytidine
CN102850418B (en) * 2011-06-30 2016-01-06 杭州容立医药科技有限公司 A kind of crystallization and drying means preparing high purity azacitidine
WO2013022872A1 (en) 2011-08-10 2013-02-14 Celgene Corporation Gene methylation biomarkers and methods of use thereof
EP2758067A1 (en) 2011-09-23 2014-07-30 Celgene Corporation Romidepsin and 5 - azacitidine for use in treating lymphoma
WO2013049093A1 (en) 2011-09-26 2013-04-04 Celgene Corporation Combination therapy for chemoresistant cancers
TW201700103A (en) 2011-11-01 2017-01-01 西建公司 Methods for treating cancers using oral formulations of cytidine analogs
EA028462B1 (en) 2012-02-24 2017-11-30 СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи Methods for treating advanced non-small cell lung cancer using tor kinase inhibitor combination therapy
SI2833905T1 (en) 2012-04-04 2018-08-31 Halozyme, Inc. Combination therapy with hyaluronidase and a tumor-targeted taxane
CN102702292B (en) * 2012-05-20 2015-04-29 湖州展望药业有限公司 Preparation method of azacitidine
CN103524584A (en) * 2012-07-05 2014-01-22 天津九海医药科技有限公司 Synthetic method of azacitidine
US9968627B2 (en) 2013-03-26 2018-05-15 Celgene Corporation Solid forms comprising 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one and a coformer, compositions and methods of use thereof
CA2925727C (en) 2013-10-10 2021-10-19 Medical Components, Inc. Huber needle assembly with safety capture device
CN104672289A (en) * 2013-11-29 2015-06-03 南京圣和药业股份有限公司 Preparation method of azacitidine impurity
US20150359810A1 (en) 2014-06-17 2015-12-17 Celgene Corporation Methods for treating epstein-barr virus (ebv) associated cancers using oral formulations of 5-azacytidine
IL277320B2 (en) 2014-08-29 2023-03-01 Medical Components Inc Huber safety needle
USD804021S1 (en) 2015-02-27 2017-11-28 Medical Components, Inc. Huber safety needle
USD804022S1 (en) 2015-02-27 2017-11-28 Medical Components, Inc. Huber safety needle
JP7033061B2 (en) 2015-10-15 2022-03-09 アジオス ファーマシューティカルズ， インコーポレイテッド Combination therapy to treat malignant tumors
KR20180064529A (en) 2015-10-15 2018-06-14 셀진 코포레이션 Combination Therapy for the Treatment of Malignant Tumors
JP6896753B2 (en) 2016-03-18 2021-06-30 メデイカル コンポーネンツ，インコーポレーテツド Hoover needle assembly
CN109651451B (en) * 2017-10-10 2023-07-11 芜湖先声中人药业有限公司 Azacitidine derivative preparation method and application thereof
US20190351031A1 (en) 2018-05-16 2019-11-21 Halozyme, Inc. Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20
CN112300222B (en) * 2020-11-26 2023-03-21 北京益佰医药研究有限公司 Azacitidine refining method with high purity and low solvent residue

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3817980A (en) * 1970-03-14 1974-06-18 Schering Ag 5-azapyrimidine nucleosides
US6642206B2 (en) * 1996-10-16 2003-11-04 Icn Pharmaceuticals, Inc. Monocyclic L-nucleosides, analogs and uses thereof

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1050899A (en) 1963-12-22
CH527207A (en) 1968-05-08 1972-08-31 Ceskoslovenska Akademie Ved Process for the preparation of 1-glycosyl-5-azacytosines
CH507969A (en) 1968-11-12 1971-05-31 Ceskoslovenska Akademie Ved Process for the preparation of 1-glycosyl-5-azacytosines
FR2123632A6 (en) 1971-01-26 1972-09-15 Ceskoslovenska Akademie Ved Prepn of 5-azacytosines and 5-azacytidines - from bis trimethylsilyl-5-azacytosine
DE2122991C2 (en) 1971-05-04 1982-06-09 Schering Ag, 1000 Berlin Und 4619 Bergkamen Process for the preparation of cytosine and 6-azacytosine nucleosides
DE2508312A1 (en) 1975-02-24 1976-09-02 Schering Ag NEW PROCESS FOR THE PRODUCTION OF NUCLEOSIDES
DE2757365A1 (en) 1977-12-20 1979-06-21 Schering Ag NEW PROCESS FOR THE PRODUCTION OF NUCLEOSIDES
US6943249B2 (en) * 2003-03-17 2005-09-13 Ash Stevens, Inc. Methods for isolating crystalline Form I of 5-azacytidine
US7038038B2 (en) * 2003-03-17 2006-05-02 Pharmion Corporation Synthesis of 5-azacytidine
US6887855B2 (en) * 2003-03-17 2005-05-03 Pharmion Corporation Forms of 5-azacytidine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3817980A (en) * 1970-03-14 1974-06-18 Schering Ag 5-azapyrimidine nucleosides
US6642206B2 (en) * 1996-10-16 2003-11-04 Icn Pharmaceuticals, Inc. Monocyclic L-nucleosides, analogs and uses thereof

Also Published As

Publication number Publication date
US20060247432A1 (en) 2006-11-02
US20040186283A1 (en) 2004-09-23
WO2004082618A2 (en) 2004-09-30
US20090005551A1 (en) 2009-01-01
US7858774B2 (en) 2010-12-28
US8058424B2 (en) 2011-11-15
US20120029181A1 (en) 2012-02-02
US20110092694A1 (en) 2011-04-21
US7038038B2 (en) 2006-05-02

Similar Documents

Publication Publication Date Title
WO2004082618A3 (en) Synthesis of 5-azacytidine
WO2002010361A1 (en) α-ISOMALTOSYLGLUCOSACCHARIDE SYNTHASE, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
AU2003270751A1 (en) Methods to increase nucleotide signals by raman scattering
WO2007011696A8 (en) Compositions and methods for coupling a plurality of compounds to a scaffold
WO2002070533A3 (en) Method for the synthesis of 2',3'-dideoxy-2',3'-didehydronucleosides
WO2008034158A3 (en) Method for producing 2-o-glyceryl-alpha-d-glucopyranoside
EG24519A (en) A method of increasing the total or soluble carbohydrate content or sweetness of an endogenous carbohydrate by catalyzing the conversion of an endogenous sugar to an alien sugar
AU3764901A (en) Process for producing, methods and compositions of glucuronoxylomannan as nutriceutical agent from higher basidiomycetes mushroom
WO2009112951A3 (en) Mutants of glycoside hydrolases and uses thereof for synthesizing complex oligosaccharides and disaccharide intermediates
WO2008073960A3 (en) Oligonucleotides containing high concentrations of guanine monomers
EP0884384A3 (en) Heat-resistant amylomaltase
WO2004050663A3 (en) An improved process for the preparation of cefuroxime sodium
NO20081868L (en) Process for producing sucrose-6-acetate by whole-cell biocatalysis
WO2000053737A3 (en) Mitomycin biosynthetic gene cluster
AU2003283217A1 (en) Method for determing predisposition to manifestation of immune system related diseases
WO2007144780A3 (en) Processes for preparing ezetimibe and intermediate compounds useful for the preparation thereof
Litjens et al. An expedient synthesis of the repeating unit of the acidic polysaccharide of the bacteriolytic complex of lysoamidase
WO2005054159A3 (en) Process for the preparation of xylene by the catalytic dehydrocyclization of diisobutylene
WO2003087107A3 (en) Method for producing halosilanes by impinging microwave energy
AU2002238521A1 (en) Compound suitable for use as a catalyst or for producing a catalyst system derived from a bis-phosphorinane
WO2007054483A8 (en) Preparation of catalysts
WO2008136199A1 (en) Process for producing withanolide
WO2007091040A3 (en) The preparation of thiosugars and their use
Ruhela et al. A facile and novel route to the antigenic branched phosphoglycan of the protozoan Leishmania major parasite
AU2360100A (en) Process for addition of haloalkanes to alkenes catalyzed by an organophosphite compound

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase